Nogo-B receptor is necessary for cellular dolichol biosynthesis and protein N-glycosylation

Dolichol monophosphate (DolP) functions as an obligate glycosyl carrier lipid in protein glycosylation reactions. DolP is synthesized by the successive condensation of isopentenyl diphosphate (IPP), with farnesyl diphosphate catalysed by a cis-isoprenyltransferase (cis-IPTase) activity. Despite the recognition of cis-IPTase activity 40 years ago and the molecular cloning of the human cDNA encoding the mammalian enzyme, the molecular machinery responsible for regulating this activity remains incompletely understood. Here, we identify Nogo-B receptor (NgBR) as an essential component of the DolP biosynthetic machinery. Loss of NgBR results in a robust deficit in cis-IPTase activity and DolP production, leading to diminished levels of dolichol-linked oligosaccharides and a broad reduction in protein N-glycosylation. NgBR interacts with the previously identified cis-IPTase hCIT, enhances hCIT protein stability, and promotes DolP production. Identification of NgBR as a component of the cis-IPTase machinery yields insights into the regulation of dolichol biosynthesis. The EMBO Journal (2011) 30, 2490-2500. doi: 10.1038/emboj.2011.147; Published online 13 May 2011